Low-grade inflammation has been related to obesity, insulin resistance, and related metabolic disorders. In this context, the -174G>C gene polymorphism of the proinflammatory interleukin 6 (IL-6) cytokine has also been associated with these diseases. Based on this, the aim of the current study was to evaluate the role of IL-6 -174G>C polymorphism in the risk of developing metabolic alterations in people with excessive body weight. One hundred six Caucasian volunteers (body mass index, 33.2 +/- 5.3 kg/m(2)) were recruited to assess the potential relationship between carrying the -174G>C polymorphism and the risk of developing obesity-related metabolic disorders, such as hypertension, atherogenic dyslipidemia, and insulin resistance evaluated by the homeostasis model assessment of insulin resistance index. Subjects carrying the C allele showed higher plasma insulin concentrations and systolic blood pressure than homozygotes for the G allele. A multiple regression analysis showed that the presence of the C allele induced an increase in the homeostasis model assessment of insulin resistance index as compared with GG subjects (adjusted R(2) = .26, P < .001). Analyzing the mentioned obesity-related diseases, an enhanced prevalence of presenting high risk of developing these complications was found for the GC and CC genotypes relative to GG, with an adjusted odds ratio of 5.2 (P = .003). This association remained significant after controlling for multiple comparisons by the 10,000-permutation test (P = .004838). These data demonstrate that the occurrence of C allele of IL-6 -174 G>C gene polymorphism in people with excessive body weight is accompanying a higher risk of developing obesity-related metabolic disorders, especially insulin resistance.